双组分调控系统介导革兰阴性菌耐药的作用机制

菌群耐药已成为临床上亟待解决的关键问题,特别是革兰阴性菌引起的耐药现象尤为突出,给临床治疗带来了巨大的挑战,尽快阐明重要细菌复杂耐药表型的调控机制就显得尤为重要。双组分调控系统(two-component regulatory systems,TCS)存在于多种革兰阴性菌中,在细菌诸多生命活动中发挥关键作用,是细菌感知环境变化并产生相应调控的主要机制之一。TCS通常由两种蛋白组成,包括感受器蛋白(通常是组氨酸激酶)和反应调节蛋白(通常是转录因子),二者可通过磷酸化介导的协同作用,整合细菌周围的环境信号、调节细菌相关的基因表达及改变细菌的某些生理行为。近年来,探索细菌TCS介导的耐药性应答机制已成为一个新的研究热点。基于此,本文从TCS介导临床重要革兰阴性菌耐药的结构基础和作用机理等方面进行综述,以期增进对细菌TCS的全面认识,为今后临床上药物的科学研发提供新的思路和对策。     

大环内酯类抗生素对细菌生物被膜作用的研究进展

细菌生物被膜(BBF)是一类由生物大分子包裹细菌而形成的具有特殊复杂结构的微克隆多细胞群体,由其感染所引起的疾病具有迁延不愈、反复发作等特点,在临床上有较大危害性。当前临床上用于治疗细菌生物被膜疾病的药物主要集中于大环内酯类抗生素,文章综述了细菌生物被膜结构特点和大环内酯类抗生素的药效动力学,并将大环内酯类抗生素清除、抑制细菌生物被膜的主要机理归纳为阻碍细菌黏附过程、破坏细菌生物被膜基础结构和干扰细菌的群体感应系统。     

细菌黏附素研究进展

黏附素是细菌表面某种特定的蛋白质结构或糖脂成分,可存在于细菌的细胞壁、外膜蛋白、鞭毛、菌毛及微毛等结构中。近年来关于细菌黏附素的研究取得了一些进展,笔者主要从细菌黏附素的发现、黏附现象及其机理、主要的一些细菌黏附素与黏附素受体、细菌黏附素研究的应用等方面作一综述。     

兽医微生物学与免疫学的成就

兽医微生物学发展的现代水平同普通微生物学和医学微生物学在研究微生物细胞微小结构和特殊机能方面的成就是分不开的。例如,关于微生物细胞膜和细胞壁结构的基础研究,不仅判定了全群微生物或细菌细胞染色特性的差别,而且可以确定抗菌物质如青     

细菌人工染色体载体系统在反向遗传学中的应用研究进展

细菌人工染色体是近十几年来发展起来的一种新型DNA克隆载体系统,具有操作简单、遗传稳定、容量大等明显的优势。论文主要综述了细菌人工染色体载体系统在基础研究、基因治疗及病毒载体疫苗等反向遗传学方面的研究进展。     

细菌多糖的生物合成机制研究进展

多糖是细菌细胞的主要组成部分,在细菌与宿主的相互作用中起到重要作用,在参与细菌与宿主的识别,帮助细菌产生毒力,调节宿主免疫反应等生物过程中扮演着重要的角色。随着基因组学的发展,人们发现尽管细菌多糖的种类很多,但它们的合成机制具有相似性。多糖生物合成的研究主要基于基因组的序列分析预测,结合代谢产物研究的基因分析,不够详尽。随着研究的深入,人们越来越关注细菌多糖的合成机制,这种机制的研究将为进一步阐明细菌多糖多样性的形成机制及与宿主间的相互作用机制奠定基础,为开发针对相应病原菌的新型疫苗和治疗方法,及进一步实现分子水平的相关疾病防控和资源开发提供技术支持。作者以肽聚糖、O-抗原和夹膜多糖为代表,阐述了其生物合成及体外生物合成机制的研究进展和相关问题,并总结了细菌多糖合成途径的研究在寻找候选抗原和控制病原细菌靶位以及研究细菌遗传进化和生物合成方面的作用。     

应对细菌耐药策略研究进展

细菌耐药性与畜牧产业发展、人类公共卫生安全和食品安全密切相关。细菌产生耐药的机制复杂,除由人-动物-环境三者之间复杂作用引起外,抗生素的使用对细菌耐药性的产生和传播具有非常重要的影响,需要采取多种策略应对细菌耐药性的产生。新发展的药物理论及分子生物学等技术的兴起,极大地推动了对细菌耐药机制的认识、新型抗菌药物的发现及药物的合理使用,为控制细菌耐药性的产生提供了重要的理论依据和技术手段。当前,细菌耐药性已然是不可忽视的严重问题,引起了多方关注。细菌耐药机制的复杂性及新药研发的困难性,决定了必须通过多种方法、多种途径和多种角度开展研究,从而控制其进一步发展。基于目前的研究现状,笔者归纳总结了多种应对细菌耐药的策略及方法,重点从新型抗菌药的研发、联合用药、药代动力学-药效动力学同步模型及多组学技术等方面阐述其在应对细菌耐药性方面的作用,以期为减缓和控制细菌耐药性的产生及临床治疗细菌感染提供参考和指导。     

高原环境下两种变异L型细菌的分离培养及鉴定

研究高原环境下L型变异细菌的变异量和抗原特征,以期为高原家畜L型细菌引发相关性疾病的临床诊治及有效预防奠定基础.选用藏系绵羊消化道食糜、藏系绵羊鼻液、西藏黄牛粪便为分离培养对象,采用特殊培养基分离培养、染色镜检、生化鉴定、血清型鉴定及PCR检测方法进行相关性研究.结果表明:L型大肠杆菌在高渗XLD培养基上呈现3种菌落形...     

机器学习方法在预测细菌耐药表型中的应用

随着我国经济迅速发展和医疗需求不断增长,人医临床、宠物临床和畜牧养殖行业中抗菌药物的使用愈发频繁,导致病原菌耐药问题日趋严峻,造成公共卫生安全隐患。快速、准确的细菌耐药表型检测能够有效指导临床医生对感染性疾病的诊断和治疗,降低由经验用药和不合理用药引发的耐药风险。然而,现有检测技术耗时较长且操作繁琐,难以在临床中推广,种类单一的快速检测试剂等产品又无法满足临床的多元化需求。因而,亟需开发新的技术方法以提供快速鉴定细菌耐药表型的有效解决方案。细菌的组学信息中蕴含大量与细菌耐药表型相关的特征,从中快速、准确地挖掘相关信息能够为快速诊断和治疗提供帮助。机器学习模型在处理复杂结构数据方面有显著优势,在挖掘组学信息工作中展示巨大应用潜力。随着该领域的快速发展,机器学习方法有望为临床快速、准确地预测耐药表型提供技术支持,助力医生诊疗准确性的提升。本综述系统总结了机器学习模型在细菌耐药表型预测领域的研究现状和发展趋势,并比较了不同机器学习方法的特点和性能,同时归纳总结细菌耐药表型预测建模工作所需的关键要素,为后续相关研究提供参考。     

喹诺酮类药物的抗菌活性与细菌耐药性研究进展

喹诺酮类药物（quinolones,QLs）是一类化学合成的抗菌药物,曾在世界范围内广泛应用于临床细菌病的治疗。其作用靶点为细菌DNA螺旋酶和拓扑异构酶,形成药-酶-DNA三元复合体,阻止蛋白质合成,从而达到抑菌效果。目前,通过对许多三元复合体的晶体结构解析,以及非催化镁离子模型的建立,进一步合理地解释了喹诺酮类药物活性受到影响的现象。临床常见致病菌对喹诺酮类药物产生耐药现象的机理研究较多,主要是基因突变、膜对药物的通透性改变及质粒介导的喹诺酮耐药性（PMQR）3个方面。文章主要对喹诺酮类药物的作用机制和细菌耐药机理进行综述,以期为后期喹诺酮类药物结构优化提供更多的信息支持。     

多杀性巴氏杆菌外膜蛋白免疫作用研究进展

外膜蛋白是细胞膜中的一种重要成分之一,在免疫方面的作用越来越受到关注.随着对多杀性巴氏杆菌外膜蛋白免疫原性及保护性的深入研究,开发有效的多杀性巴氏杆菌外膜蛋白疫苗将成为可能.笔者等就具有免疫作用的多杀性巴氏杆菌外膜蛋白的研究进展情况进行综述.     

Outer membrane protein profiles of Yersinia ruckeri

The outer membrane protein (OMP) profiles of 135 isolates of Yersinia ruckeri, obtained from nine European countries (100 isolates), North America (23 isolates), Australia (six isolates) and South Africa (two isolates), and including four reference strains, were examined by SDS-PAGE. Outer membranes were isolated by selective solubilisation of the cytoplasmic membrane with 0.5% (w/v) sodium N-lauroyl sarcosinate (Sarkosyl). Outer membrane proteins were stable after in vitro passage and there was no variation in OMP profiles due to colony selection. With the exception of a 39.5 kDa peptidoglycan-associated protein there was also no variation at different stages of the growth cycle. The 39.5 kDa protein was not produced during logarithmic growth phase but increased in abundance as the stationary phase progressed. Interstrain variation occurred in the possession of a 36.5 or 38 kDa heat-modifiable protein and in the possession of peptidoglycan-associated proteins in the molecular weight range 36.5 to 40.5 kDa. Based on variation of these proteins five OMP-types, designated OMP-types 1-5, were identified among the 135 isolates examined. Outer membrane protein analysis was demonstrated to be useful in epidemiological studies of Y. ruckeri.     

具有免疫作用的多杀性巴氏杆菌外膜蛋白特性研究

外膜蛋白是细胞膜的重要成分之一,在免疫方面的作用日益受到关注,对其深入研究可使开发有效的多杀性巴氏杆菌外膜蛋白疫苗成为可能,本文就多杀性巴氏杆菌概况、组成及具有免疫作用的外膜蛋白的特性进行综述,以期推动多杀性巴氏杆菌疾病的诊断和防治。     

兔源高致病性大肠杆菌外膜蛋白型的差异性分析

从山东某地区大、中型兔场连续三年(2002-2004年)分离、鉴定的43株高致病性 大肠杆菌体内提取外膜蛋白(OMP),测定其外膜蛋白型(OMPs),通过SDS-PAGE分析,比 较不同年份间高致病性大肠杆菌分离株的外膜蛋白型。结果表明:三年共产生了三种OMP型 (A-C)。且在同年份内具有多样性,不同年份之间具有差异性。     

Use of membrane proteins from Salmonella gallinarum for prevention of fowl typhoid infection in chickens

Outer membrane protein isolated from Salmonella gallinarum was examined at different concentrations with or without a mineral-oil adjuvant for its immunogenicity and protection against live challenge. A formalin-killed whole-cell bacterin of the same organism was used for comparison. The results suggested that membrane proteins from S. gallinarum give better protection than formalin-killed whole-cell bacterin. Addition of an oil adjuvant to the protein appeared to increase the efficiency of the vaccine. When protein was given to chickens at 400 micrograms/100 g of live body weight, it produced 100% protection against oral challenge with S. gallinarum.     

Outer membrane protein profiles of Edwardsiella ictaluri from fish.

Outer membrane proteins (OMP) prepared with sodium N-lauroyl sarcocinate (SLS) from 33 Edwardsiella ictaluri isolates from fish were examined by electrophoresis. Twenty-eight isolates from channel catfish (Ictalurus punctatus) had similar OMP profiles. Ten bands (71 kilodaltons [kD] to 19.5 kD) were identified in all isolates from channel catfish. One major 35-kD protein comprised most of the protein content of the outer membrane of isolates from channel catfish. Differences existed among isolates in the amount of protein within minor OMP bands. Edwardsiella ictaluri ATCC 33202 contained larger quantities of the 38.5- and 37-kD proteins than did the other isolates. Outer membrane protein profiles of E ictaluri derived from Bengal danio (Danio devario) and walking catfish (Clarias batrachus) were identical to OMP profiles of isolates from channel catfish. In contrast, OMP profiles from single isolates from green knife fish (Eigemannia virescens) and white catfish (Ictalurus catus) were different. Variations in incubation time, SLS extraction time, SLS extraction number, and in vivo and in vitro passage had no effect on the OMP profile of E ictaluri ATCC 33202. An increase in duration of sample solubilization did affect the OMP profile of E ictaluri ATCC 33202 by decreasing the amount of protein in 52-, 46-, and 43.5-kD bands. Accompanying the decrease were increased staining intensity in the 31.5- and 28.5-kD bands and the appearance of 4 new bands (34, 33, 25.5, and 22.5 kD). Edwardsiella ictaluri, a gram-negative bacterium in the family Enterobacteriaceae, is the cause of enteric septicemia of catfish.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outer membrane protein antigens of Moraxella bovis

Outer membranes were isolated from bovine isolates and type strains of Moraxella bovis, M phenylpyruvica, M lacunata, and M ovis by sodium N lauroyl sarcosinate extraction and differential centrifugation. Analysis of outer membranes from these organisms by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis revealed that all M bovis isolates shared a common polypeptide pattern that was readily distinguishable from other Moraxella spp. Nine major outer membrane protein bands were identified by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis analysis of M bovis. Immunoblotting of protein antigens of M bovis revealed several outer membrane proteins that seemed to be common antigens of all M bovis isolates.     

Characterisation of the outer membrane protein antigens of British field isolates of Moraxella bovis

Outer membranes of a single isolate of Moraxella bovis were prepared and their purity evaluated by a comparison of the iodinated proteins from whole cells and on outer membranes. The protein patterns of the outer membranes of 10 isolates were examined by SDS-polyacrylamide gel electrophoresis, and the antigenic relationship between proteins of different isolates determined by immunoblotting, using antiserum produced against the outer membrane of the single isolate of M. bovis. The overall protein pattern of the different isolates was similar although not identical, but, significantly, only three separate immunogenic proteins were common to all the isolates under examination.     

革兰氏阴性菌外膜蛋白研究进展

外膜蛋白对细菌本身和宿主都具有重要的作用。本文综述了革兰氏阴性菌外膜蛋白的组成、结构、功能及遗传调控,外膜蛋白可作为大肠杆菌的克隆标志,在细菌的致病机理及免疫机理中都有重要作用,研制开发外膜蛋白疫苗具有广阔的应用前景,必将为细菌性疾病的防治提供有力的措施。     

牛布氏杆菌PCR检测方法的建立

根据GenBank上公布的牛布氏杆菌外膜蛋白OMP31的基因序列设计特异性引物,对牛布氏杆菌样品进行PCR扩增并将产物克隆到pMD18-T载体后测序。结果表明,扩增的目的片段大小为602 bp,与预期扩增序列同源性为99.7％;该PCR检测体系的特异性强,不能在非布氏杆菌 DNA中扩增出条带;敏感性高,最低检测的DNA含量为0.9 pg/μL。该检测体系的成功构建为牛布氏杆菌病的检测、鉴定和流行病学调查提供了有力的技术支持。